Glutamine preferentially inhibits T‐helper type 2 cell‐mediated airway inflammation and late airway hyperresponsiveness through the inhibition of cytosolic phospholipase A₂ activity in a murine asthma model

Abstract

Gln was found to be effective in the suppression of Th2-dependent phenotypes and late AHR, and this effect of Gln appeared to be at least partially attributable to its ability to suppress cLPA(2) activity in the airway. Our results suggest that clinical use of Gln for patients with asthma may be beneficial.

Mechanism of glutamine inhibition of cytosolic phospholipase a2 (cPLA2): Evidence of physical interaction between glutamine-Induced mitogen-activated protein kinase phosphatase-1 and cPLA2

“…Both MKP-1 induction and MKP-1 mediated p38 dephosphorylation within 5 min following Gln administration, suggesting that Gln dephosphorylated cPLA 2 indirectly through MKP-1-mediated p38 dephosphorylation. However, Gln dephosphorylated p-cPLA 2 rapidly within 5 min, as in the case of p38 in LPS-injected mice [13,14,20], suggesting that phosphatase is involved. Gln injection resulted in a rapid induction of MKP-1 within 5 min, which coincided with Gln-induced dephosphorylation of cPLA 2 (Fig.…”

“…We have reported previously a beneficial effect of Gln on allergic asthma in mice [14,20]. In this study, we assessed whether cPLA 2 /MKP-1 linkage was involved in the beneficial effect of Gln.…”

“…AHR was determined as changes in airway function after challenge by aerosolized methacholine using published procedures [14,19]. After methacholine challenge, airway resistance (RL) data were collected continuously.…”

“…Gln was dissolved in sterilized distilled water to 3%. A volume of 0Á5 ml (750 mg/ kg) [12][13][14][15] was administered intraperitoneally (i.p.) 10 min before or 10 min after LPS injection.…”

“…To understand the molecular mechanism of Gln antiinflammatory activity, we have shown that Gln can protect animals effectively from endotoxin shock as well as inhibit bronchial allergic asthma by inhibiting cPLA 2 phosphorylation [13,14]. To decipher the mechanism of Gln inhibition of cPLA 2 , we demonstrated recently that Gln deactivated p38 and Janus kinase (JNK) mitogenactivated protein kinases (MAPKs) by rapidly inducing MAPK phosphatase (MKP)-1 protein [15], which preferentially dephosphorylated p38 and JNK [16,17], suggesting that Gln inhibited cPLA 2 phosphorylation indirectly by blocking the kinase activity of p38, a major upstream pathway for cPLA 2 phosphorylation [18].…”